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Exploring the Possibility of Excited State Keto‐Enolate Transformation of the Oxyluciferin‐Luciferase Complex with QM/MM Free Energy Simulations
Author(s) -
Chung Seyoung,
Choi Sun Mi,
Rhee Young Min
Publication year - 2019
Publication title -
chemphotochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 18
ISSN - 2367-0932
DOI - 10.1002/cptc.201900114
Subject(s) - qm/mm , protonation , bioluminescence , chemistry , quantum yield , transformation (genetics) , chemical physics , energetics , computational chemistry , physics , molecular dynamics , thermodynamics , quantum mechanics , ion , organic chemistry , biochemistry , fluorescence , gene
Firefly bioluminescence has been widely studied due to its high quantum yield and its broad range of color modulation, but debates on the origin of its color modulation and the exact chemical form of the emitter are still ongoing. Herein, the keto‐enolate transformation of the oxyluciferin–luciferase complex is investigated using quantum mechanics/molecular mechanics (QM/MM) free energy simulations. We find that the free energy profile of this transformation largely depends on the protonation state of the phenoxy oxygen in oxyluciferin. Although the keto‐enolate transformation can be facilitated by protonation of this oxygen atom, the overall transformation is still unlikely and only the keto form will predominantly exist along our hypothesized reaction path. Nevertheless, we show with additional calculations with a modestly modified protein electric field that the energetics of the transformation can be heavily modulated with the protein electrostatics. This suggests that carefully modeling the protein–ligand interaction is key to understanding the reaction mechanism of the firefly bioluminescence and that it is not yet appropriate to completely rule out the possibility of having enolate participation.